mGluR5 shows a characteristic desensitization which modulates the response of a cell to neurotransmitter release. The presence of several MAPK consensus sites in the C-terminal tail of mGluR5 suggests that MAPK may play a role in modulation of mGluR5 desensitization. We propose to study the functional significance of MAPK activity on mGluR5 function. We will first analyze desensitization of mGluR5 in the presence and absence of MEK inhibitors and then determine at what sites MAPK may be functioning to affect the desensitization of mGluR5. Finally, we will determine which of the identified sites has functional relevance and is responsible for the effects we see on mGluR5 desensitization.